This disclosure relates to novel melatonin analogues or naphthyl(ethyl)acetamides, their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a dual melatoninergic agonist and serotoninergic antagonist.
Agomelatine, known by the chemical name N-[2-(7-methoxy-1-napthyl)ethyl]acetamide, acts by stimulating MT1 and MT2 receptors and blocking 5-HT2B and 5-HT2C receptors.
Agomelatine is currently in phase III clinical trials for major depressive disorder (http://clinicaltrials.gov/ct/show/NCT00411099) and has been indicated as useful in the treatment of bipolar disorder, sleep disorder, and anxiety (WO2005002562; and WO 2005077887).
Active metabolites of Agomelatine include the following:

Agomelatine has been found to have a side effect profile similar to placebo. (Loo, H et al., Int J Neuropsychopharmacol, 2002, 5(Suppl. 1):Abst P.3.E.033).
Despite its apparent efficacy, it is desirable to provide a compound that has the beneficial activities of Agomelatine and may also have other benefits, e.g., reduced adverse side effects, with a decreased metabolic liability, to further extend its pharmacological effective life, enhance patient compliance and, potentially, to decrease population pharmacokinetic variability and/or decrease its potential for dangerous drug-drug interactions.